CX3CR1+ c-kit+ bone marrow cells give rise to CD103+ and CD103- dendritic cells with distinct functional properties.
Dendritic cells (DC) represent a rather heterogeneous cell population with regard to morphology, phenotype, and function and, like most cells of the immune system, are subjected to a continuous renewal process. CD103(+) (integrin alpha(E)) DC have been identified as a major mucosal DC subset involved in the induction of tissue-specific homing molecules on T cells, but little is known about progenitors able to replenish this DC subset. Herein we report that lineage (lin)(-)CX(3)CR1(+)c-kit(+) (GFP(+)c-kit(+)) bone marrow cells can differentiate to either CD11c(+)CD103(-) or CD11c(+)CD103(+) DC in vitro and in vivo. Gene expression as well as functional assays reveal distinct phenotypical and functional properties of both subsets generated in vitro. CD103(-) DC exhibit enhanced phagocytosis and respond to LPS stimulation by secreting proinflammatory cytokines, whereas CD103(+) DC express high levels of costimulatory molecules and efficiently induce allogeneic T cell proliferation. Following adoptive transfer of GFP(+)c-kit(+) bone marrow cells to irradiated recipients undergoing allergic lung inflammation, we identified donor-derived CD103(+) DC in lung and the lung-draining bronchial lymph node. Collectively, these data indicate that GFP(+)c-kit(+) cells contribute to the replenishment of CD103(+) DC in lymphoid and nonlymphoid organs.
del Rio
Maria-Luisa
ML
Institute of Immunology, Hannover Medical School, Hannover, Germany.
Rodriguez-Barbosa
Jose-Ignacio
JI
Bölter
Jasmin
J
Ballmaier
Matthias
M
Dittrich-Breiholz
Oliver
O
Kracht
Michael
M
Jung
Steffen
S
Förster
Reinhold
R
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism*; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology; D000073883:CX3C Chemokine Receptor 1; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D039001:Integrin alpha Chains / Q000096:biosynthesis* / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis* / Q000235:genetics; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics
D015703:Antigens, CD; D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D039001:Integrin alpha Chains; D019707:Receptors, Chemokine; C091367:alpha E integrins; D019009:Proto-Oncogene Proteins c-kit